Mutational analysis of two positional candidate susceptibility genes for bipolar disorder on chromosome 12q23-q24: phenylalanine hydroxylase and human LIM-homeobox LHX5.

Abstract

In the search for chromosome 12 genes potentially involved in the pathogenesis of bipolar disorder we will screen Phenylalanine hydroxylase and human LIM-homeobox LHX5 genes for sequence variants, both of which have been suggested as candidate genes. The genes lie on chromosome 12q23-24, near the Darier's disease gene, ATP2A2. We have previously reported two families in which the pattern of segregation of illness is consistent with genetic linkage between this chromosomal region and a putative highly penetrant autosomal dominant major affective disorder locus (pedigree 324, maximum LOD=2.1; pedigree 5501, maximum LOD=3.6). We screened the coding and intronic flanking regions of the phenylalanine hydroxylase and LHX5 genes for sequence variation by denaturing high-performance liquid chromatography in individuals from the pedigrees. In total, nine single nucleotide polymorphisms and one 6 base pair deletion were identified. Our studies allowed us to conclude that none of these variants act as a highly penetrant autosomal dominant susceptibility locus for mood disorder in our families.